The two phases of the clinical validation of preclinical translational mechanistic research on PDE5 inhibitors since Viagra’s advent.

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The two phases of the clinical validation of preclinical translational mechanistic research on PDE5 inhibitors since Viagra’s advent. A personal perspective





The first phase: the vasodilator action of on demand administration of PDE5 inhibitors for erectile dysfunction (ED)


The second phase: the antifibrotic/smooth muscle protective action of continuous long term administration (CLTA) of PDE5 inhibitors for corporal Veno-occlusive dysfunction (CVOD) and Peyronie’s disease (PD)



*In summary,
extensive evidence supports CLTA of PDE5i to halt or reverse fibrosis of the penile corpora cavernosa and tunica albuginea. Such treatment is expected to result in permanently improved erectile function for many (although not all) ED patients, and to finally offer a non-surgical option or as a co-adjuvant for the treatment of PD. Human studies have supported some of these preclinical findings and their interpretation, but their discussion is beyond the scope of this paper, although some reviews from other authors have stated the relevance of a primarily anti-fibrotic PDE5i strategy for the treatment of PD, coupled with its smooth muscle protection action for the treatment of CVOD, and lower urogenital tract symptoms (LUTS), mainly in the context of daily PDE5i [22–28]. We look forward to seeing what new advances of PDE5i preclinical and clinical research will bring for their use as an anti-fibrotic and smooth muscle protective therapeutic approach, often coupled to stem cell treatment, not just for these conditions, but in other chronic serious fibrotic processes in various urological and non-urological conditions [17, 29–33].
 

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  • 10.1038@s41443-018-0076-9The two phases of the clinical validation.pdf
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